Heterotaxy, visceral, 6, autosomal

Summary

Heterotaxy, visceral, 6, autosomal (MONDO:0013887) is a disease caused by CFAP53 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CFAP53 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 78

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	heterotaxy, visceral, 6, autosomal
Mondo ID	MONDO:0013887
OMIM	614779
DOID	DOID:0051020
UMLS	C3553676
MedGen	766590
GARD	0024961
Is cancer (heuristic)	no

Also known as: heterotaxy, visceral, 6, autosomal · heterotaxy, visceral, 6, autosomal recessive · HTX6

Data availability: 78 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › visceral heterotaxy › heterotaxy, visceral, 6, autosomal

Related subtypes (18): right atrial isomerism, situs inversus, heterotaxy, visceral, 1, X-linked, laterality defects, autosomal dominant, heterotaxy, visceral, 2, autosomal, heterotaxy, visceral, 3, autosomal, heterotaxy, visceral, 4, autosomal, heterotaxy, visceral, 7, autosomal, heterotaxy, visceral, 8, autosomal, dextrocardia, levocardia, heterotaxy, visceral, 9, autosomal, with male infertility, heterotaxy, visceral, 10, autosomal, with male infertility, heterotaxy, visceral, 11, autosomal, with male infertility, heterotaxy, visceral, 5, autosomal, heterotaxy, visceral, 12, autosomal, heterotaxy, visceral, 13, autosomal, heterotaxy, visceral, 14, autosomal

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

78 retrieved; paginated sample, class counts are floors:

30 uncertain significance, 24 likely benign, 9 benign, 6 likely pathogenic, 5 benign/likely benign, 2 pathogenic, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
208550	NM_145020.5(CFAP53):c.121C>T (p.Arg41Ter)	CFAP53	Pathogenic	no assertion criteria provided
2914683	NM_145020.5(CFAP53):c.1004_1008del (p.Met335fs)	CFAP53	Pathogenic	criteria provided, single submitter
2441724	NM_145020.5(CFAP53):c.877C>T (p.Gln293Ter)	CFAP53	Likely pathogenic	criteria provided, single submitter
37014	NM_145020.5(CFAP53):c.1213+1G>A	CFAP53	Likely pathogenic	criteria provided, single submitter
3714503	NM_145020.5(CFAP53):c.474-2A>G	CFAP53	Likely pathogenic	criteria provided, single submitter
3765586	NM_145020.5(CFAP53):c.1214-1G>A	CFAP53	Likely pathogenic	criteria provided, single submitter
3779510	NM_145020.5(CFAP53):c.1144G>T (p.Glu382Ter)	CFAP53	Likely pathogenic	criteria provided, single submitter
4748875	NM_145020.5(CFAP53):c.996+1G>C	CFAP53	Likely pathogenic	criteria provided, single submitter
767053	NM_145020.5(CFAP53):c.1513C>T (p.Arg505Cys)	CFAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
969306	NM_145020.5(CFAP53):c.1101C>A (p.Asp367Glu)	CFAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030233	NM_145020.5(CFAP53):c.1411C>T (p.Arg471Ter)	CFAP53	Uncertain significance	criteria provided, single submitter
1043108	NM_145020.5(CFAP53):c.1475C>T (p.Ser492Phe)	CFAP53	Uncertain significance	criteria provided, single submitter
1057411	NM_145020.5(CFAP53):c.1213+4A>G	CFAP53	Uncertain significance	criteria provided, single submitter
1057622	NM_145020.5(CFAP53):c.781A>G (p.Ser261Gly)	CFAP53	Uncertain significance	criteria provided, single submitter
1374764	NM_145020.5(CFAP53):c.1153G>T (p.Ala385Ser)	CFAP53	Uncertain significance	criteria provided, single submitter
1392383	NM_145020.5(CFAP53):c.1541C>A (p.Pro514Gln)	CFAP53	Uncertain significance	criteria provided, single submitter
1403920	NM_145020.5(CFAP53):c.121C>G (p.Arg41Gly)	CFAP53	Uncertain significance	criteria provided, single submitter
1418796	NM_145020.5(CFAP53):c.772C>T (p.Leu258Phe)	CFAP53	Uncertain significance	criteria provided, multiple submitters, no conflicts
1485412	NM_145020.5(CFAP53):c.1357A>G (p.Met453Val)	CFAP53	Uncertain significance	criteria provided, single submitter
1494109	NM_145020.5(CFAP53):c.1282G>T (p.Glu428Ter)	CFAP53	Uncertain significance	criteria provided, single submitter
1512604	NM_145020.5(CFAP53):c.737A>T (p.Gln246Leu)	CFAP53	Uncertain significance	criteria provided, single submitter
1516204	NM_145020.5(CFAP53):c.413A>C (p.Lys138Thr)	CFAP53	Uncertain significance	criteria provided, single submitter
1953801	NM_145020.5(CFAP53):c.1513C>A (p.Arg505Ser)	CFAP53	Uncertain significance	criteria provided, multiple submitters, no conflicts
1966222	NM_145020.5(CFAP53):c.698G>A (p.Gly233Glu)	CFAP53	Uncertain significance	criteria provided, single submitter
2046403	NM_145020.5(CFAP53):c.1024T>C (p.Tyr342His)	CFAP53	Uncertain significance	criteria provided, single submitter
2100864	NM_145020.5(CFAP53):c.235G>C (p.Val79Leu)	CFAP53	Uncertain significance	criteria provided, multiple submitters, no conflicts
2155044	NM_145020.5(CFAP53):c.146C>T (p.Ala49Val)	CFAP53	Uncertain significance	criteria provided, single submitter
217132	NM_145020.5(CFAP53):c.472A>G (p.Arg158Gly)	CFAP53	Uncertain significance	criteria provided, multiple submitters, no conflicts
2442192	NM_145020.5(CFAP53):c.553G>A (p.Ala185Thr)	CFAP53	Uncertain significance	criteria provided, multiple submitters, no conflicts
2506009	NM_145020.5(CFAP53):c.1318C>T (p.Arg440Cys)	CFAP53	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CFAP53	Strong	Autosomal recessive	heterotaxy, visceral, 6, autosomal	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFAP53	Orphanet:101063	Situs inversus totalis
CFAP53	Orphanet:157769	Situs ambiguus

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CFAP53	HGNC:26530	ENSG00000172361	Q96M91	Cilia- and flagella-associated protein 53	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFAP53	Cilia- and flagella-associated protein 53	Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CFAP53	Transcription factor	no		CFAP53/TCHP, TPH_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
bronchus	1
left testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFAP53	194	broad	marker	bronchial epithelial cell, bronchus, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFAP53	1,448

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFAP53	Q96M91	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
epithelial cilium movement involved in determination of left/right asymmetry	1	1296.3×	0.003	CFAP53
manchette assembly	1	1296.3×	0.003	CFAP53
sperm flagellum assembly	1	674.1×	0.003	CFAP53
cilium movement	1	391.9×	0.004	CFAP53
determination of left/right symmetry	1	255.3×	0.005	CFAP53
flagellated sperm motility	1	117.0×	0.010	CFAP53
cilium assembly	1	73.6×	0.014	CFAP53

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CFAP53	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CFAP53

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CFAP53	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.